High blood lead levels are among the most prevalent childhood conditions and the most prevalent environmental threat to the health of children in the United States" (HEALTHY PEOPLE 2000, p. 319). Toxicity from lead can be manifested in virtually every organ system. Lead and other heavy metals interfere with normal Ca2+ metabolism. Perturbation of Ca2+ metabolism has severe consequences on salivary gland function, amelogenesis. and dentinogenesis. Once lead enters the cell, its toxic effects are most likely mediated by activating protein kinase C and/or Ca2+ calmodulin- dependent protein kinase by modifying reactive sulfhydryl groups or by binding to Ca2+ binding sites on ion transporters. Salivary gland hypofunction is clearly related to increased caries. Lead may affect cariogenesis directly by competing for calcium binding sites, thereby affecting demineralization and remineralization of enamel. Lead in saliva and plaque may result in the formation of lead fluoride which is essentially insoluble, rendering fluoride unavailable for its caries protective effect. We propose determining the influence of prenatal exposure to lead on susceptibility to dental caries and also explore the effect of lead on salivary gland development and function as determined by induced flow rate and selected organic and inorganic constituents. Calcium metabolism subsequent to lead and heavy metal exposure will be monitored by observing steps involved in stimulation-induced [Ca2+) mobilization in salivary acinar cells by measuring: l) inositol phosphate formation, 2) intracellular Ca2+ release, and 3) divalent cation influx. Possible influence of lead and heavy metals on Ca2+-regulated ion transport mechanisms associated with fluid secretion will be determined by assaying intracellular pH [Cl-] and [Na+]. Knowledge gained from these studies could have a major societal impact, enhance our understanding of the etiology and pathogenesis of dental caries, and the effects of lead and heavy metals on salivary gland physiology.